The thermodynamic properties of small nonelectrolytes in salt solutions will be investigated, particularly those compounds whose study elucidates the mechanism of interaction of salts with proteins. These studies will involve the determination of free energies and enthalpies of transfer of nonelectrolytes from water to salt solutions by electrochemical and calorimetric techniques. The effects of electrolytes on protein conformation will be investigated. Both difference spectroscopy and Raman spectroscopy will be employed, the latter to obtain information about groups which change their environment during the course of protein denaturation. These results will be combined with the data obtained for the small model compounds to develop a quantitative thermodynamic interpretation of protein denaturation by electrolytes. The denaturation of proteins by transition metal and heavy metal cations and complex anions at low denaturant concentrations will be studied over a wide pH range. The aim will be to correlate the effects of possible trace pollutants in water on protein stability.